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Transketolase deficiency in adipose tissues protects mice from diet-induced obesity by promoting lipolysis

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posted on 2020-04-15, 21:47 authored by Ada AdminAda Admin, Na Tian, Qi Liu, Yakui Li, Lingfeng Tong, Ying Lu, Yemin Zhu, Ping Zhang, Hanbei Chen, Lei Hu, Jian Meng, Ming Feng, Minle Li, Liang Zheng, Bin Li, Tianle Xu, Lifang Wu, Xuemei Tong

Obesity has recently become a prevalent health threat worldwide. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and obesity, the role of transketolase (TKT), an enzyme in the non-oxidative branch of the PPP which connects PPP and glycolysis, remains obscure in adipose tissues. In this study, we specifically delete TKT in mouse adipocytes and find no obvious phenotype upon normal diet feeding. However, adipocyte TKT abrogation attenuates high fat diet (HFD)-induced obesity, reduces hepatic steatosis, improves glucose tolerance, alleviates insulin resistance and increases energy expenditure. Mechanistically, TKT deficiency accumulates non-oxidative PPP metabolites, decreases glycolysis and pyruvate input into the mitochondria, leading to increased lipolytic enzyme gene expression and enhanced lipolysis, fatty acid oxidation and mitochondrial respiration. Therefore, our data not only identify a novel role of TKT in regulating lipolysis and obesity, but also suggest limiting glucose-derived carbon into the mitochondria induces lipid catabolism and energy expenditure.

Funding

This work was supported by grants from National Natural Science Foundation of China (81672322, 81972210 and 31601118); National Key R&D Program of China (2019YFA0906100), National Key Research and Development Program of China (No. 2016YFC1304800), The Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning and Construction Plan of Laboratory Technical Team in Shanghai Universities (SYjdyx18007).

History

References

https://doi.org/10.2337/DB19-1087

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Diabetes

Keywords

adipose tissue Diet-Induced Obesity mice lipolysis Transketolase deficiency Biological Sciences not elsewhere classified

Licence

CC BY-NC-SA 4.0